Table 3.
ROR for hepatic injury of individual drugs ranked by absolute number of cases (with at least 30 cases) in population <18 years old
| ROR (95% CI) | |||||
|---|---|---|---|---|---|
| With vaccines | Without vaccines | ||||
| Number of cases = 6595 | Number of cases = 6147 | ||||
| Drug | Number of cases | Number of non-cases | Crude | Adjusted* | Adjusted* |
| Isotretinoin | 420 | 12 051 | 3.4 (3.1, 3.8) | 1.9 (1.7, 2.1) | 1.3 (1.1, 1.5) |
| Paracetamol | 347 | 4 049 | 8.4 (7.7, 9.3) | 6.0 (5.4, 6.8) | 3.4 (3.1, 3.8) |
| Valproic acid | 208 | 3 065 | 6.5 (5.8, 7.4) | 4.0 (3.5, 4.7) | 2.2 (1.9, 2.6) |
| Carbamazepine | 140 | 2 271 | 5.9 (5.1, 6.8) | 3.6 (3.0, 4.3) | 2.1 (1.8, 2.5) |
| Methotrexate | 134 | 1 873 | 6.8 (5.9, 7.9) | 4.2 (3.5, 5.1) | 2.5 (2.1, 3.0) |
| Minocycline | 117 | 959 | 11.6 (10.0, 13.5) | 4.3 (3.5, 5.3) | 3.5 (2.9, 4.3) |
| Lamotrigine | 112 | 3 005 | 3.5 (3.0, 4.2) | 2.2 (1.8, 2.7) | 1.3 (1.1, 1.6) |
| Zidovudine | 106 | 2 446 | 4.1 (3.4, 4.9) | 4.5 (3.7, 5.5) | 1.2 (1.0, 1.5) |
| Pemoline† | 104 | 282 | 35.1 (30.5, 40.4) | 31.6 (25.0, 40.0) | 14.4 (11.5, 18.2) |
| Ceftriaxone | 104 | 1 695 | 5.8 (4.9, 6.9) | 5.0 (4.0, 6.1) | 2.6 (2.1, 3.2) |
| Methylphenidate | 96 | 4 199 | 2.2 (1.8, 2.6) | 1.3 (1.0, 1.6) | 0.7 (0.6, 0.9)‡ |
| Bosentan | 85 | 353 | 22.8 (19.4, 26.9) | 15.0 (11.8, 19.2) | 7.3 (5.7, 9.2) |
| Ciclosporin | 71 | 117 | 5.7 (4.6, 7.1) | 3.0 (2.4, 3.9) | 1.6 (1.3, 2.1) |
| Atomoxetine | 64 | 1 624 | 3.7 (2.9, 4.7) | 2.0 (1.5, 2.6) | 1.3 (1.0, 1.6) |
| Azithromycin | 63 | 2 932 | 2.0 (1.6, 2.6) | 1.8 (1.4, 2.3) | 0.8 (0.6, 1.0)‡ |
| Olanzapine | 62 | 845 | 6.9 (5.5, 8.7) | 3.1 (2.4, 4.0) | 2.3 (1.7, 2.9) |
| Erythromycin | 60 | 1 196 | 4.7 (3.7, 6.0) | 4.2 (3.2, 5.5) | 2.3 (1.8, 3.1) |
| Infliximab | 60 | 2 083 | 2.7 (2.1, 3.5) | 1.3 (1.0, 1.7) | 0.9 (0.7, 1.1)‡ |
| Risperidone | 59 | 2 611 | 2.1 (1.7, 2.7) | 1.0 (0.8, 1.4)‡ | 0.7 (0.5, 0.9‡) |
| Phenytoin | 57 | 1 222 | 4.4 (3.4, 5.6) | 3.0 (2.3, 4.0) | 2.0 (1.5, 2.6) |
| Voriconazole | 52 | 270 | 18.2 (14.7, 22.5) | 10.7 (7.9, 14.6) | 6.7 (5.0, 9.1) |
| Topiramate | 51 | 1 356 | 3.5 (2.7, 4.6) | 2.1 (1.6, 2.8) | 1.1 (0.9, 1.5)‡ |
| Sulfamethoxazole/trimethoprim | 48 | 3 064 | 1.5 (1.1, 2.0) | 1.3 (1.0, 1.7) | 0.9 (0.7, 1.2)‡ |
| Isoniazid | 47 | 140 | 31.7 (25.7, 39.1) | 23.8 (16.7, 33.7) | 14.0 (9.9, 19.7) |
| Vincristine | 46 | 1 119 | 3.9 (2.9, 5.1) | 2.7 (2.0, 3.7) | 1.5 (1.1, 2.0) |
| Lamivudine | 45 | 764 | 5.6 (4.2, 7.3) | 4.9 (3.6, 6.6) | 1.7 (1.3, 2.3) |
| Ethinylestradiol/levonorgestrel | 43 | 928 | 4.4 (3.3, 5.8) | 1.9 (1.4, 2.6) | 1.5 (1.1, 2.1) |
| Oxcarbazepine | 43 | 1 205 | 3.4 (2.5, 4.5) | 1.9 (1.4, 2.6) | 1.1 (0.8, 1.5)‡ |
| Gemtuzumab | 42 | 241 | 16.4 (12.9, 20.9) | 17.1 (12.3, 24.0) | 6.7 (4.8, 9.4) |
| Fluconazole | 42 | 409 | 9.7 (7.5, 12.5) | 8.6 (6.2, 12.0) | 3.6 (2.6, 5.0) |
| Mercaptopurine | 41 | 252 | 15.3 (12.0, 19.6) | 11.4 (8.1, 16.0) | 6.0 (4.3, 8.4) |
| Phenobarbital | 41 | 594 | 6.5 (4.9, 8.6) | 6.6 (4.8, 9.2) | 3.9 (2.8, 5.4) |
| Amoxicillin/clavulanate potassium | 38 | 1 309 | 2.7 (2.0, 3.7) | 1.7 (1.2, 2.3) | 0.8 (0.6, 1.2)‡ |
| Tioguanine | 37 | 240 | 14.5 (11.2, 18.9) | 14.5 (11.2, 18.9) | 6.2 (4.4, 8.8) |
| Rifampicin | 37 | 243 | 14.3 (11.0, 18.6) | 8.3 (5.8, 12.0) | 5.1 (3.6, 7.3) |
| Nevirapine | 37 | 1 487 | 2.3 (1.7, 3.2) | 2.8 (2.0, 3.9) | 0.8 (0.6, 1.1)‡ |
| Cytarabine | 36 | 885 | 3.8 (2.8, 5.2) | 2.9 (2.1, 4.1) | 1.5 (1.1, 2.2) |
| Clozapine | 36 | 1 646 | 2.1 (1.5, 2.8) | 0.8 (0.6, 1.1)‡ | 0.7 (0.5, 0.9)‡ |
| Clarithromycin | 35 | 1 081 | 3.0 (2.2, 4.2) | 1.8 (1.3, 2.5) | 1.0 (0.7, 1.4)‡ |
| Interferon beta | 30 | 497 | 5.7 (4.1, 7.9) | 4.4 (3.0, 6.5) | 2.3 (1.6, 3.3) |
| Acetylsalicylic acid | 30 | 1 070 | 2.6 (1.9, 3.7) | 1.3 (0.9, 1.9)‡ | 0.9 (0.6, 1.3)‡ |
The following drugs had more than 30 cases but were not associated with hepatic injury: Hepatitis B vaccine, ibuprofen, poliovirus vaccine live oral, measles, mumps and rubella vaccine, diphtheria and tetanus toxoids and pertussis, sertraline, haemophilus B conjugate vaccine.
*
Adjusted for gender, age, country, and type of reporter.
†
Drugs withdrawn from the market due to hepatotoxicity.
‡
Adjusted RORs not statistically significant.